Does clomethiazole cause pathological liver test values?/nA female patient has been prescribed Hemi

Fråga: Does clomethiazole cause pathological liver test values? A female patient has been prescribed Heminevrin (clomethiazole), one tablet in the morning and two tablets at night, for treatment of anxiety due to dementia. After 3-4 weeks of treatment elevated liver test values were revealed, ASAT 1.4 (reference value <0.7) and ALAT 4.4 (reference value <0.7). ALP and bilirubin values were normal. Do these findings necessitate withdrawal of Heminevrin, which is the only treatment that helps this patient.

Sammanfattning: We found no case reports of pathological liver test values caused by clomethiazole in literature, although in this case a connection cannot be excluded. Therefore we recommend withdrawal of clomethiazole, alternatively a reduced dose.

Svar: An extensive literature searh in the databases Medline, Swedis and common pharmacological handbooks, has not revealed any reports of clomethiazole causing pathological liver test values.

The only literature found concerned farmacokinetic data in patients with liver cirrhosis treated with clomethiazole (1,2). The pharmacokinetics of clomethiazole were studied in 8 patients with advanced cirrhosis of the liver and in 6 healthy volunteers after oral and intravenous administration of the drug. The systemic bioavailability of oral clomethiazole increased about tenfold, whereas its elimination was only slightly retarded. Clomethiazole undergoes extensive first pass metabolism in the liver and the increased bioavailability was clearly due to decreased first-pass metabolism of clomethiazole in the cirrhotic liver. The results indicate that clomethiazole should be used in reduced dosage when given by mouth to patients with cirrhosis of the liver.

Nine cases of liver influence possibly caused by clomethiazole have been reported to the Swedish Adverse Drug Reactions Committe (SADRAC), 1966-1995. They are as follows: one case of necrosis of the liver, one case of jaundice, two cases of pathological liver test values, four cases of mixed liver reaction and one case of elevated amylase. In none of the cases is clomethiazole the only suspected drug.

We suggest the incidence be reported to the regional SADRAC.